Department of Cardiology, Sackler Faculty of Medicine, Tel Aviv University, 6997801, Ramat Aviv, Israel.
Cardiovasc Diabetol. 2021 Nov 24;20(1):225. doi: 10.1186/s12933-021-01412-5.
Incretin hormones are peptides released in the intestine in response to the presence of nutrients in its lumen. The main incretins are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). GLP-1 stimulates insulin secretion, inhibits glucagon secretion at pancreatic α cells and has also extrapancreatic influences as slowing of gastric emptying which increases the feeling of satiety. GIP is the main incretin hormone in healthy people, causative of most the incretin effects, but the insulin response after GIP secretion in type 2 diabetes mellitus (T2DM) is strongly reduced. Therefore, in the past GIP has been considered an unappealing therapeutic target for T2DM. This conception has been changing during recent years, since it has been reported that resistance to GIP can be reversed and its effectiveness restored by improving glycemic control. This fact paved the way for the development of a GIP receptor agonist-based therapy for T2DM, looking also for the possibility of finding a combined GLP-1/GIP receptor agonist. In this framework, the novel dual GIP and GLP-1 receptor agonist tirzepatide seems to be not just a new antidiabetic medication. Administered as a subcutaneous weekly injection, it is a manifold single pharmacological agent that has the ability to significantly lower glucose levels, as well as improve insulin sensitivity, reduce weight and amend dyslipidemia favorably modifying the lipid profile. Tirzepatide and additional dual GLP-1/GIP receptor agonists that could eventually be developed in the future seem to be a promising furthest advance for the management of several cardiometabolic settings. Obviously, it is too early to be overly hopeful since it is still necessary to determine the long-term effects of these compounds and properly verify the potential cardiovascular benefits. Anyway, we are currently facing a novel and very appealing therapeutic option.
肠促胰岛素激素是肠道在腔内容物存在时释放的肽类物质。主要的肠促胰岛素包括胰高血糖素样肽-1（GLP-1）和葡萄糖依赖性胰岛素释放肽（GIP）。GLP-1 刺激胰岛素分泌，抑制胰岛α细胞分泌胰高血糖素，还具有胰腺外作用，如减缓胃排空，从而增加饱腹感。GIP 是健康人的主要肠促胰岛素激素，引起大多数肠促胰岛素作用，但 2 型糖尿病（T2DM）患者 GIP 分泌后的胰岛素反应强烈降低。因此，在过去，GIP 一直被认为是 T2DM 不太吸引人的治疗靶点。近年来，这种观念发生了变化，因为有报道称，通过改善血糖控制，可以逆转 GIP 抵抗并恢复其效力。这一事实为基于 GIP 受体激动剂的 T2DM 治疗铺平了道路，同时也在寻找可能发现 GLP-1/GIP 受体双重激动剂。在这一框架内，新型双重 GIP 和 GLP-1 受体激动剂替西帕肽似乎不仅仅是一种新型抗糖尿病药物。作为每周皮下注射给药，它是一种具有多种单一药理作用的药物，能够显著降低血糖水平，改善胰岛素敏感性，减轻体重，并通过有利地改善血脂谱来纠正血脂异常。替西帕肽和未来可能开发的其他双重 GLP-1/GIP 受体激动剂似乎是管理多种心血管代谢情况的一个有前途的进一步进展。显然，现在过于乐观还为时过早，因为仍需要确定这些化合物的长期效果，并适当验证其潜在的心血管益处。无论如何，我们目前面临着一种新的、非常有吸引力的治疗选择。
